Cartilage degenerative diseases like rheumatoid arthritis (RA) and osteoarthritis (OA) have age, obesity and inflammation as causal risk factors however the precise molecular mechanisms underlying these risk factors are ill understood. No disease-modifying drug is available for OA while the drugs available for RA are not equally effective for all patients. An increased molecular understanding of the causal factors will therefore be beneficial for both diseases.
Very few studies have systematically evaluated the age-dependent changes in human tissues including cartilage due to the limited availability. Such studies are particularly pertinent for cartilage since cartilage regeneration is inefficient even in healthy young adults often leading to OA although pediatric populations demonstrate superior cartilage repair. Recently, allogeneic juvenile cartilage (from donors less than 13 years of age) has even been successfully utilized for repair of focal cartilage defects. Upon phenotypic and functional characterization of juvenile and adult chondrocytes, it was found that juvenile chondrocytes demonstrated increased cell proliferation and ECM generation as compared to the adult chondrocytes. The molecular factors responsible for these functional differences that define the regenerative capacity of juvenile and adult chondrocytes have however not been characterized.
Another key question that remains unanswered is how age-related changes modulate the cell and tissue-specific response to inflammation. Inflammaging, i.e., a systemic upregulation of inflammatory cues with aging, is a well-documented phenomenon. For example, plasma levels of the pro-inflammatory cytokine IL-6 are low in young adults and begin to increase in healthy people at about 50-60 years of age (Ershler (1993) J. Am. Geriatr. Soc. 41(2):176-181). Inflammaging is associated with many forms of age-related pathologies, such as neurodegeneration, atherosclerosis, metabolic syndrome, diabetes mellitus and musculoskeletal system (i.e. osteoporosis, OA and RA). However, since age dependent tissue-specific changes are not well understood, it remains unclear whether the age-related changes in tissues render them increasingly susceptible to the inflammaging cues thereby leading to a synergistic increase in inflammation-mediated damage in aging tissues.
There remains a need for improved cell-based therapies for repair and regeneration of cartilage for treating bodily injuries and diseases involving cartilage degeneration.